Next Generation Sequencing in Diagnosis of MLPA Negative Cases Presenting as Duchenne/ Becker Muscular Dystrophies

Excerpt

To the Editor: Duchenne and Becker muscular dystrophies (dystrophinopathies) are common neuromuscular disorders affecting about 1 in 3500 live male births [1] and are characterized by proximal myopathy, resulting in difficulty in getting up from sitting position and climbing stairs with calf hypertrophy and positive Gower sign. Deletions and duplications of one or more exons of dystrophin gene account for approximately 60%–70% [85% in case of Becker Muscular Dystrophy (BMD)] and 5–10% of pathogenic variants respectively [2]. Multiplex ligation probe amplification (MLPA) is the most cost and labour-efficient method to detect deletions / duplication. If MLPA does not find any deletion/ duplication there is a possibility of single nucleotide variants (small deletions or insertions, single-base changes, and splice site changes) or there can be an alternative diagnosis. Common differential diagnosis are Limb girdle muscular dystrophy (LGMD), Emery Dreifuss muscular dystrophy (EDMD) and collagen 6 myopathies [3]. …